Risks of Macrosomia Associated with Catechol-O-Methyltransferase Genotypes and Genetic-Epigenetic Interactions among Children with and without Gestational Diabetes Exposure.

Background: Gestational diabetes mellitus (GDM) is a major macrosomia risk factor. Variations in the catechol-O-methyltransferase (COMT; rs4680) genotypes are associated with heightened susceptibility to environmental exposures and nutritional conditions. However, macrosomia risks associated with COMT genetics, epigenetics, and the interaction between genetic and epigenetics among children with and without exposure to GDM are unknown. Methods: Data from women/children pairs (n = 1087) who participated in the Tianjin Gestational Diabetes Birth Cohort were used to examine the odds of being born with macrosomia associated with COMT-genotypes, 55 CpG sites located on the COMT gene, and genetic and epigenetic interactions. Odds of macrosomia associated with COMT genetic, epigenetic, genetic and epigenetic interactions, and moderations with GDM were tested using adjusted logistic regression models. Results: Overall, 16.1% (n = 175) of children were born with macrosomia. Models showed that children with at least one copy of the minor allele (A) had higher odds of macrosomia (odds ratio, 1.82; 95% confidence interval 1.25-2.64) compared with children with the GG-genotype. After false discovery rate corrections, none of the 55 CpG sites located on the COMT gene was associated with odds of macrosomia. The genetic and epigenetic associations were not modified by exposure to GDM. Conclusion: Findings suggest carriers of the COMT GG-genotype had lower odds of macrosomia, and this association was not modified by epigenetics or exposure to GDM.